The Notch signaling pathway has been implicated in cell fate decisions mediated by cell-cell interactions via the Notch receptor and the Notch ligands Delta and Serrate/Jagged, which were initially discovered in Drosophila, for example, as described by Six, et al., 2003; and Han and Moore, 2000. Notch signaling has been found to be conserved in mammalian systems, and has been implicated in a number of important cell functions, as described in, for example, de la Pompa, et al., 1997; Apelqvist, et al., 1999; Singh, et al., 2000; Post, et al., 2000; Tezuka, et al., 2002; and Grandbarbe, et al., 2003.
Six, E. et al. (2003) have described a murine ligand Delta1 (Dll1) that was cleaved at a cleavage site 10 aa N-terminal to the TM domain, between His-535 and Met-536. Han, et al., 2000 isolated a cDNA clone encoding a human homolog of the mouse Delta-like-1 gene, designated human Delta-like-1 (hDll1). They artificially created a soluble form, hDll1NDSL, which contained the DSL domain and its adjacent N-terminal 50 amino acids (aa 127-225), and expressed and purified this molecule from bacteria as a glutathione S-transferase (GST) fusion protein. No naturally occurring soluble human Delta-like-1 protein has to date been identified or isolated.